CN103599117A - Use of szechuan melandium root pentacyclic triterpenoid saponin compound in preparation of drug for reducing blood sugar - Google Patents

Use of szechuan melandium root pentacyclic triterpenoid saponin compound in preparation of drug for reducing blood sugar Download PDF

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CN103599117A
CN103599117A CN201310627408.7A CN201310627408A CN103599117A CN 103599117 A CN103599117 A CN 103599117A CN 201310627408 A CN201310627408 A CN 201310627408A CN 103599117 A CN103599117 A CN 103599117A
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pentacyclic triterpene
triterpene saponins
melandrii szechuanensis
radix melandrii
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CN103599117B (en
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王学勇
赵保胜
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Abstract

The invention relates to a use of a szechuan melandium root pentacyclic triterpenoid saponin compound in preparation of a drug for reducing blood sugar. Through massive screening and research, the inventor first finds the szechuan melandium root pentacyclic triterpenoid saponin compound extracted from a caryophyllaceae plant szechuan melandium root, purifies it and especially finds that a composition of a compound with sinocrassuloside as a mother nucleus and the szechuan melandium root pentacyclic triterpenoid saponin compound has strong blood sugar-reduction effects and can be used for preparation of anti-diabetic drugs.

Description

Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is prepared the purposes of hypoglycemic drug
Technical field
The present invention relates to Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds and prepare the purposes of hypoglycemic drug, belong to Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds new medical use field.
Background technology
Diabetes are diseases that a kind of carbohydrate metabolism disturbance causes, and it shows as during fasting state or oral glucose tolerance test and gives after glucose, and plasma glucose levels raises, and occurs hyperglycemia.Diabetes are mainly divided into two classes, be type 1 diabetes (insulin dependent diabetes mellitus (IDDM), insulin-dependent diabetes mellitus, IDDM) and type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus, non-insulin-dependent diabetes mellitus, NIDDM).The amount that produces insulin in type 1 diabetes patient body reduces, and does not even produce insulin, and insulin is mainly responsible for regulating the utilization of body glucose, and it produces to reduce and makes blood sugar increasing.2 type glycosurias are mainly relevant with the factor such as insulin resistant (IR).Type 2 diabetes mellitus patient has hyperinsulinemia conventionally, occurs plasma insulin level rising symptom.Insulin resistant (IR) means that in patient's body, main insulin sensitivity tissue comprises that liver, muscle and fatty tissue have produced opposing to insulin stimulating glucose and lipometabolic effect.The consequence that produces glucose opposing is that patient's body compensates insulin resistant by secreting more insulin, and even so, improper rising has still appearred in the glucose level in patient's blood plasma.
Antidiabetic medicine has several to select, except insulin, widely used chemicals has short islet secretion agent sulfonylurea, and such medicine is secreted more islets of langerhans by stimulating pancreas beta cell and usually improved the insulin level in blood plasma, but has the risk that causes patient's hypoglycemia.The widely used hypoglycemic medicine of an other class is biguanides, as metformin and phenformin, if this class drug main promotes the utilization of body human peripheral blood sugar, its advantage is to carry out certain correction to hyperglycemia level, but can not increase hypoglycemic risk, can combine use with insulin or insulin succagoga, but exist, cause lactic acidosis and diarrhoea, nauseating side effect.The newer hypoglycemic medicine of an other class is euglycemic agent glitazone (thiazolidinediones), represent that medicine has rosiglitazone and pioglitazone, this class medicine can increase the sensitivity of tissue to insulin, improve cell the utilization of glucose is brought into play to hypoglycemic effect, can obviously reduce fasting glucose and insulin, post-prandial glycemia and insulin are also had to obvious reducing effect, but also have untoward reaction such as causing water-sodium retention, blood volume increase and cardiac load increase.
The anti-diabetic activity screening substances of plant origin is the important channel that a Novel antidiabetic is excavated.In the research of anti-diabetic activity screening substances, saponins compound progressively enters research staff's the visual field.Saponin component can be by regulating blood fat, improve insulin resistant, reducing the approach preventions such as blood glucose and treatment diabetes.The more Saponin with hypoglycemic activity of research mainly contains at present: arasaponin, Spica Prunellae triterpenoid saponin, ginsenoside, olive Saponin, momordica saponins, Cortex araliae chinensis Saponin etc., above-mentioned result of study shows that Saponin has good blood sugar lowering application and development potentiality.
Radix Melandrii szechuanensis is the dry root of Caryophyllaceae (Caryophyllaceae) silene plant Yunnan Rhizoma Cynanchi Stauntonii (Silene viscidula Franch.), the merit with analgesia, hemostasis, heat clearing away, diuresis, is mainly used in treating the diseases such as traumatic injury, rheumatic ostalgia, bronchitis, urinary tract infection.The research of Radix Melandrii szechuanensis at present mainly concentrates on chemical constitution study aspect, and the research report of pharmacology aspect is less.The main chemical composition of Radix Melandrii szechuanensis has saponins, protein-based, organic acid, polysaccharide, cyclic peptide etc., and applicant is through the separated following a few saponins constituents that has of determining structure at present: comprise saponin sinocrassuloside VI, sinocrassuloside VII, sinocrassuloside VIII, sinocrassuloside IX, sinocrassuloside XII, sinocrassuloside X III etc.; Cyclic peptide composition, comprises Radix Melandrii szechuanensis cyclic peptide A, B, C(silenins A, B, C); Ketosteroid composition, comprises 20-HE, 1-epi-integristerone A, abutasterone, stachysterone A, 15-hydroxyl stachysterone A; Organic acid composition, comprises p-hydroxycinnamic acid, oleanolic acid, vanillic acid etc.
Summary of the invention
Technical problem to be solved by this invention is to provide the purposes that Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is prepared hypoglycemic drug, present inventor is through magnanimity screening and research, find first to extract the Pentacyclic triterpene saponins compounds that purification obtains from pinkwort Radix Melandrii szechuanensis, the compound that the sinocrassuloside of particularly take is parent nucleus, the compositions of above-claimed cpd and the plant extract that contains Sinocrassuloside compound have stronger blood sugar decreasing effect, can be used in and prepare antidiabetic medicine.
The compound that the sinocrassuloside of take is parent nucleus comprises trim and the derivant that contains sinocrassuloside mother nucleus structure, comprising: the aglycon of sinocrassuloside compound and with the saponin of different numbers and structure glucose.Mainly refer to sinocrassuloside VI, sinocrassuloside VII, sinocrassuloside VIII, sinocrassuloside IX, sinocrassuloside X, sinocrassuloside XI, sinocrassuloside XII, sinocrassuloside X III and above-claimed cpd pharmaceutically acceptable salt.
Wherein, sinocrassuloside VI and sinocrassuloside VII, sinocrassuloside VIII and sinocrassuloside IX, sinocrassuloside XII and sinocrassuloside X III are cis-trans-isomer, six kinds of compositions all have stronger hypoglycemic activity, embody certain structure activity relationship.
Pharmaceutically acceptable salt of the present invention refers to the formed salt of sinocrassuloside compound and alkali or alkaline-earth metal, and alkali comprises sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium bicarbonate, ammonium chloride or ammonia; Alkaline-earth metal comprises sodium, potassium, calcium, aluminum, copper, zinc or magnesium.
The Pentacyclic triterpene saponins compounds that the present invention protects and analog thereof mainly extract from plant Radix Melandrii szechuanensis, and the Pentacyclic triterpene saponins compounds that still extraction from other plant, chemosynthesis, mode semi-synthetic or biotransformation obtain and analog thereof are also within protection scope of the present invention.
Pentacyclic triterpene saponins compounds is mainly used in treating non-insulin-dependent diabetes mellitus (type 2 diabetes mellitus), but is not limited to this, dosage range: 0.1～10mg/kg the weight of animals.
The technical scheme that the present invention solves the problems of the technologies described above is as follows: Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is prepared the purposes of hypoglycemic drug, and the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure BDA0000424928050000031
Wherein, R 1for H, Ac, Glc(glucose, glucose) in a kind of;
R 2a kind of in (E)-MC, (Z)-MC, Ac;
R 3for H, Xyl(Xylose, xylose) in a kind of;
R 4for H, CH 3, CH 2cH 2cH 2cH 3in a kind of;
The structural formula of above-mentioned Ac is as follows:
The structural formula of above-mentioned (E)-MC is as follows:
Figure BDA0000424928050000042
The structural formula of above-mentioned (Z)-MC is as follows:
Figure BDA0000424928050000043
On the basis of technique scheme, the present invention can also do following improvement.
Further, the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure BDA0000424928050000044
Further, the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure BDA0000424928050000051
Further, the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure BDA0000424928050000052
Further, the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure BDA0000424928050000061
Further, the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure BDA0000424928050000062
Further, the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure BDA0000424928050000071
Further, the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Further, the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure BDA0000424928050000081
Further, described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds can be used separately, two or more mixing is used or mixes use with other adjuvants, makes the injection, externally used solution agent, unguentum, paste, patch, drop, gargarism, suppository, sublingual tablet, sticking tablet, membranous patch, aerosol, effervescent tablet, the drop pill that use clinically;
Further, described injection comprises the multiple injecting pathways such as intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection and intracavitary administration;
Further, described externally used solution agent is lotion or liniment;
Further, described unguentum is ointment or plaster;
Further, described drop is eye drop or nasal drop;
Further, described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds can be used separately, two or more mixing is used or mixes use, food prepared therefrom or beverage with other adjuvants.
The invention has the beneficial effects as follows:
The invention provides Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds and prepare the purposes of hypoglycemic drug, the compound that the sinocrassuloside of particularly take is parent nucleus and the compositions of above-claimed cpd have significant anti-diabetic activity, can effectively reduce the glucose-tolerant ability of blood glucose and/or raising body.
Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds provided by the invention, the plant source blood sugar lowering Compound Phase ratio of the compound that the sinocrassuloside of particularly take is parent nucleus and the compositions of above-claimed cpd and existing report, have hypoglycemic effect obviously, act on strong feature.
Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds provided by the invention, the compound that the sinocrassuloside of particularly take is parent nucleus and the compositions of above-claimed cpd are compared with existing blood sugar lowering chemicals, there is chemical skeleton structure unique novel, preparation technology is simple, pollute little, the strong and little feature of side effect of blood sugar reducing function.
In addition, Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds provided by the invention, the compound that the sinocrassuloside of particularly take is parent nucleus and the compositions of above-claimed cpd are except the medicine of the rapid onset of insulin type drug administration by injection, the natural extract chemicals that a unique drug administration by injection approach can match in excellence or beauty with insulin effect.
Accompanying drawing explanation
Fig. 1 is that different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of mouse blood sugar;
Fig. 2 is that different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of Mouse Weight;
Fig. 3 is that different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of mice food-intake;
Fig. 4 is that different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of mice amount of drinking water;
Fig. 5 is that different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of mouse blood sugar;
Fig. 6 is the blood sugar reducing function research of holding time after the drug withdrawal of different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds;
Fig. 7 is that different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of Mouse Blood insulin content;
Fig. 8 is that different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of mouse islets element sensitivity;
Fig. 9 is that different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of Mouse Liver glycogen content;
Figure 10 is that different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of Mouse Muscle glycogen content;
Figure 11 is the impacts of different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds on normal ICR Mouse Weight;
Figure 12 is the impacts of different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds on normal ICR mouse blood sugar;
Figure 13 is the impacts of different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds on T2DM rat blood sugar;
Figure 14 is the impacts of different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds on T2DM rat OGTT;
Figure 15 is the impacts of different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds on T2DM rats'liver glycogen content;
Figure 16 is the impacts of different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds on T2DM rat muscle glycogen content;
Figure 17 is the impacts of different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds on T2DM rat GSP content;
In accompanying drawing, * and Normal group comparison, p<0.05; * and Normal group comparison, p<0.01; #with model group comparison, p<0.05; ##with model group comparison, p<0.01.
The specific embodiment
Below principle of the present invention and feature are described, example, only for explaining the present invention, is not intended to limit scope of the present invention.
Extraction, separation, purification, the discrimination method of experimental example 1 Radix Melandrii szechuanensis pentacyclic triterpenoid
Get Radix Melandrii szechuanensis 21kg, after pulverizing, with 95% the ethanol of 170L and 70% ethanol, extract respectively three times, concentrate to obtain extractum 7kg, isolation and purification method reference literature (J.Zhao, Norio Nakamura, Masao Hattori.New triterpenoidsaponins from the roots of sinocrassulaasclepiadea[J] .Pharmaceutical Society of Japan, 2004, 52 (2): 230-237.) obtain macromolecular compound sinocrassuloside VI, sinocrassuloside VII, sinocrassuloside VIII, sinocrassuloside IX, sinocrassuloside XII, sinocrassuloside X III, wherein, sinocrassuloside VI and sinocrassuloside VII, sinocrassuloside VIII and sinocrassuloside IX, sinocrassuloside XII and sinocrassuloside X III are 3 pairs of cis-trans-isomers.
Compound 1 and compound 2(sinocrassuloside VI and sinocrassuloside VII): white powder, molecular formula is: C 71h 102o 31.ESI-MS（m/z）：1473.2[M+Na]+，1449.7[M-H] -。 1h-NMR and 13the concrete data of C-NMR are in Table 1.
Compound 3 and compound 4(sinocrassuloside VIII and sinocrassuloside IX): white powder, molecular formula is: C 72h 104o 31.ESI-MS（m/z）：1487.2[M+Na] +，1499.7[M+Cl] -，1463.8[M-H] -。 1h-NMR and 13the concrete data of C-NMR are in Table 1.
Compound 7 and compound 8(sinocrassuloside XII and sinocrassuloside X III): white powder, molecular formula is: C 75h 110o 31.ESI-MS（m/z）：1529.3[M+Na] +，1541.8[M+Cl] -，1505.6[M-H] -。 1h-NMR and 13the concrete data of C-NMR are in Table 1.
Figure BDA0000424928050000111
Figure BDA0000424928050000121
Figure BDA0000424928050000131
the blood sugar reducing function of experimental example 2 Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds to type 2 diabetes mellitus mice
Animal and feeding and management
12 week age male KK ay80 of mices, 12 week age, male C57BL/6 mice was 10, China biotech inc, Fukang, Beijing provides, credit number SCXK(capital) 2009-0015, mice adaptability is fed after 1 week and is carried out pharmacodynamic experiment.
Experimental animal feeding condition is as shown in table 2:
Table 2 experimental animal feeding condition
Temperature 22℃±2℃
Illumination
12 hours bright/12 are hour dark
12 hours bright/12 are hour dark: represent that the light and shade time that replaces is respectively 12 hours.
Animal feeding is raised in box in the plastics that have bedding and padding, clean level KK ayspecial-purpose high lipid food (purchased from China biotech inc, Fukang, Beijing) is fed, and freely drinks water.
Experimental design
Adaptability was fed after 1 week, 80 KK aymice is divided into 8 groups at random, is respectively model group, 1 group of compound, 2 groups of compounds, 3 groups of compounds, 4 groups of compounds, 7 groups of compounds, 8 groups of compounds and positive drug metformin group, 10 every group.10 the normal C57BL/6 mices of separately take are Normal group.KK wherein aythe special high lipid food of mice feed, the normal feedstuff of Normal group feed.Normal group, model group mouse subcutaneous injection water for injection, Radix Melandrii szechuanensis saponin is respectively organized the different saponin of mouse subcutaneous injection, positive drug metformin group gavage metformin aqueous solution, administration time is 9:00 every day left and right administration volume and is 10ml/kgBW.Continuous 2 weeks.
Mus tail blood sampling weekly, test strips method is measured blood glucose.
Grouping situation is as follows:
Table 3 animals administer and dosage
Grouping Administration Dosage (mg/kgBW)
Normal group Water for injection _
Model group Water for injection _
1 group of compound Compound 1 2.0
2 groups of compounds Compound 2 2.0
3 groups of compounds Compound 3 2.0
4 groups of compounds Compound 4 2.0
7 groups of compounds Compound 7 2.0
8 groups of compounds Compound 8 2.0
Positive drug metformin group Metformin 500
Medication
Each saponin component of Radix Melandrii szechuanensis pentacyclic triterpene is dissolved in respectively in sterile water for injection, filtration sterilization, every day subcutaneous injection; Metformin is dissolved in sterilized water, gastric infusion; Normal group, model group mice are only injected the water for injection of equal-volume (10ml/kgBW).Every morning 9 administrations, amount to 2 weeks.
Experimental program
Measure weekly mouse blood sugar one time, totally 2 times.Survey before blood glucose, mice overnight fasting, cuts tail measuring blood sugar of blood extracting.
Experiment stops: administration finishes this experimentation after (14 days) in 2 weeks.
Data statistics
Adopt SPSS10.0 software to carry out Data Management Analysis, all indexs all with mean ± standard deviation (
Figure BDA0000424928050000152
) represent, between group, relatively adopt variance analysis.
Result
Different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of mouse blood sugar
The impact of the different saponin components of the main observation of this part experiment Radix Melandrii szechuanensis pentacyclic triterpene on mouse blood sugar, relatively the blood sugar reducing function between heterogeneity is strong and weak, for follow-up work provides experimental basis.
Before administration (0 week), with blood sugar level random packet, model group and each administration group mouse blood sugar are apparently higher than Normal group, and difference has significance, and data show, KK aymouse blood sugar value is higher, is qualified diabetic mice model.
After pharmaceutical intervention 1 week, with model group comparison, each saponin component group mouse blood sugar all has reduction in various degree, wherein, compound 1 blood sugar reducing function is the strongest (with model group comparison, p<0.01), next is compound 2, compound 4, compound 3, compound 7, compound 8, wherein compound 8 shows certain blood sugar lowering trend, with model group comparison, does not occur significant difference.
In the time of 2 weeks, each administration group mouse blood sugar declines more obvious (with model group ratio, all having p<0.01), and each saponin component blood sugar reducing function of Radix Melandrii szechuanensis is strong and weak basic identical in the time of 1 week with administration, as shown in Figure 1.
Discuss
Diabetics be take blood sugar increasing as main indications, the high glucose of body persistence can bring disaster to body tissue, organ and cell, and cause the chronic complicating diseases such as diabetic nephropathy, diabetic foot, optical fundus and peripheral neuropathy, therefore, reduce the primary goal that body glucose level is treatment diabetes.
It is strong and weak that first this experiment has compared the different saponin component blood sugar reducing functions that extract from Radix Melandrii szechuanensis.Result of study shows, compound 1 and compound 2(are cis-trans-isomer) blood sugar reducing function is the strongest, next is that compound 3 and compound 4(are cis-trans-isomer), compound 7 and compound 8 blood sugar reducing functions slightly a little less than, in administration in the time of 1 week, 8 of compounds show certain blood sugar lowering trend, with the comparison of model group blood glucose, there is not significant difference, continue administration after one week, there is statistical significance in side, shows that this composition blood sugar reducing function is weaker than front 5 constituents.
Conclusion
Each saponin constituent extracting in Radix Melandrii szechuanensis has stronger hypoglycemic activity, is the desirable active component for the treatment of diabetes.
The therapeutical effect of experimental example 3 Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds to type 2 diabetes mellitus mice
Animal and feeding and management
12 week age male KK ay60 of mices, 10 (China biotech inc, Fukang, Beijing provides, credit number SCXK(capital) 2009-0015 of male C57BL/6 mice in 12 week age), adaptability is fed after 1 week and is carried out pharmacodynamic experiment.
Experimental animal feeding condition is as shown in table 4:
Table 4 experimental animal feeding condition
Temperature 22℃±2℃
Illumination
12 hours bright/12 are hour dark
12 hours bright/12 are hour dark: represent that the light and shade time that replaces is respectively 12 hours.
Animal feeding is raised in box in the plastics that have bedding and padding, clean level KK ayspecial-purpose high lipid food (purchased from China biotech inc, Fukang, Beijing) is fed, and freely drinks water.
Experimental design
Adaptability was fed after 1 week, 60 KK aymice is divided into 6 groups at random, is respectively model group, 1 group of compound, 2 groups of compounds, 3 groups of compounds, 4 groups of compounds and positive drug metformin group, 10 every group.10 the normal C57BL/6 mices of separately take are Normal group.KK wherein aythe special high lipid food of mice feed, the normal feedstuff of Normal group feed.Normal group, model group mouse subcutaneous injection water for injection, Radix Melandrii szechuanensis saponin is respectively organized the different saponin of mouse subcutaneous injection, positive drug metformin group gavage metformin aqueous solution, administration time is 9:00 every day left and right administration volume and is 10ml/kgBW.Continuous 2 weeks.
Record weekly Mouse Weight, amount of drinking water, food-intake.When experiment finishes, get blood, separation of serum, measures blood glucose, insulin content, calculates insulin sensitivity index.Get part liver, skeletal muscle, weigh to measure hepatic glycogen, muscle glycogen.
Grouping situation is as follows:
Table 5 animals administer and dosage
Grouping Administration Dosage (mg/kgBW)
Normal group Water for injection _
Model group Water for injection _
1 group of compound Compound 1 2.0
2 groups of compounds Compound 2 2.0
3 groups of compounds Compound 3 2.0
4 groups of compounds Compound 4 2.0
Positive drug metformin group Metformin 500
Medication
Compound 1, compound 2, compound 3, compound 4 are dissolved in sterile water for injection, filtration sterilization, every day subcutaneous injection, metformin gastric infusion, Normal group, model group mice are only injected the water for injection of equal-volume (10ml/kg BW).Every morning 9:00 administration, amounts to 2 weeks (14 days).
Experimental program
The mensuration of mice drinking water consumption: gravimetric method is surveyed 24 hours food-intakes of mice and amount of drinking water weekly, note reclaiming bleed raise box granule feedstuff to guarantee the accuracy of food-intake.
The mensuration of body weight: measure weekly Mouse Weight one time.
Blood specimen: measure weekly mouse blood sugar one time.Mice overnight fasting, cuts tail measuring blood sugar of blood extracting.When experiment finishes, measuring blood sugar of blood extracting, insulin, get part liver, skeletal muscle, and test kit method is measured liver/muscle glycogen content.
Experiment stops: administration finishes this experimentation after (14 days) in 2 weeks.
Data statistics
Adopt SPSS10.0 software to carry out Data Management Analysis, all indexs all with mean ± standard deviation (
Figure BDA0000424928050000171
Figure BDA0000424928050000172
) represent, between group, relatively adopt variance analysis.
Result
Different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of Mouse Weight
Model group mice compared with normal control group mice body weight gain is (all having p<0.01) obviously, and this is because KK aymice is a kind of of fat Mus, and body weight is apparently higher than due to common mice of the same age.Each compound group of Radix Melandrii szechuanensis saponin and the increase of positive drug metformin group Mouse Weight are more stable, per day growth rate is slow compared with model group, shows that Radix Melandrii szechuanensis saponin has certain inhibitory action to diabetic mice body weight gain, as shown in Figure 2, wherein, the effect of compound 1 inhibition body weight gain is the most obvious.
Different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of mice food-intake
Model group mice food-intake, apparently higher than Normal group, meets diabetes clinical " polyphagia " symptom.Giving different pharmaceutical intervened after 1 week, each is organized mice food-intake and reduces compared with model group, wherein, 1 group of compound, the feed of positive drug metformin group mice obviously reduce (with model group comparison, p<0.05), other each group only shows as minimizing trend, with model group comparison, no difference of science of statistics.
Administration is in the time of 2 weeks, and except 4 groups of compounds, other each pharmaceutical intervention group mice food-intake is compared with model group, all has obvious decline (p<0.05 or p<0.01), shows as certain time-effect relationship, as shown in Figure 3.
Different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of mice amount of drinking water
Model group mice amount of drinking water, apparently higher than Normal group, meets diabetes clinical " polydipsia " symptom.Pharmaceutical intervention is in the time of 1 week, 2 weeks, each administration group amount of drinking water all declines to some extent, with model group comparison, except 4 groups of compounds do not occur significant difference in the time of 1 week in administration, all the other are respectively organized amount of drinking water and decline all obviously (with model group comparison, p<0.05 or p<0.01), as shown in Figure 4.
Different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of mouse blood sugar
The variation of mouse blood sugar during this part experiment is observed pharmaceutical intervention respectively and after drug withdrawal.
After pharmaceutical intervention 1 week, with model group comparison, except 4 groups of compounds do not occur significant difference, all the other respectively organize blood glucose decline all obviously (with model group comparison, all having p<0.01).Administration is in the time of 2 weeks, and blood glucose decline is more obvious, and (with model group ratio, p<0.01), wherein, 1 group of mouse blood sugar of compound is lower than Normal group; Except 4 groups of compounds, other each compound hypoglycemic activity of Radix Melandrii szechuanensis saponin is all better than positive drug metformin, shows to have stronger hypoglycemic activity, as shown in Figure 5.
Meanwhile, present inventor is also studied holding time of blood sugar reducing function after the drug withdrawal of Radix Melandrii szechuanensis saponin.Result demonstration, after drug withdrawal, each administration group KK aymouse blood sugar gos up gradually, drug withdrawal is in the time of 2 weeks, and positive drug metformin group mouse blood sugar and model group be no significant difference, shows that blood sugar reducing function disappears, each administration group blood glucose of Radix Melandrii szechuanensis saponin also gos up to some extent, but still is starkly lower than model group (p<0.01).Drug withdrawal is in the time of 3 weeks, and 1 group of mouse blood sugar of compound is still starkly lower than model group, and data show, after drug withdrawal, the Radix Melandrii szechuanensis saponin blood sugar reducing function persistent period is long compared with positive drug metformin, in relatively long-time, has delayed the rise speed of blood glucose, as shown in Figure 6.
Different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of mouse islets cellulose content and insulin sensitivity (ISI)
The horizontal compared with normal matched group of model group mouse islets element increases obviously (p<0.01), but blood glucose value is higher, shows as certain insulin resistant (IR), meets type 2 diabetes mellitus model indication.After pharmaceutical intervention, except 4 groups of compounds, all the other are respectively organized mouse islets element level and obviously raise compared with model group, (p<0.05 or p<0.01), show that Radix Melandrii szechuanensis saponin has the effect that promotes beta Cell of islet insulin secretion, as shown in Figure 7.
From ISI, model group mice ISI obviously declines, each administration group mice is all significantly improved (all having p<0.01) compared with model group ISI, shows that Radix Melandrii szechuanensis saponin has the biologic activity of certain increase body insulin sensitivity, as shown in Figure 8.
Different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds are to KK aythe impact of Mouse Liver glycogen, muscle glycogen content
Data result shows, KK aymouse Liver glycogen, muscle glycogen content compared with normal matched group obviously reduce (p<0.01).After pharmaceutical intervention, each organizes Mouse Liver glycogen content all obviously increases (p<0.05 or p<0.01) compared with model group; Different Radix Melandrii szechuanensis saponin are inconsistent to the effect of muscle glycogen content influence, and wherein, compound 1,2 effects are strong (with model group comparison, p<0.01), and 3,4 groups of muscle glycogen content of compound have certain increase trend, but with model group comparison, without obvious significant difference.
This experiment shows, Radix Melandrii szechuanensis saponin can the memory function of enhancing body tissue to glycogen.Wherein, 1 group of liver of compound, the increase of muscle glycogen content are the most obvious, similar to positive drug metformin group, as shown in Fig. 9～10.
Discuss
Diabetics be take blood sugar increasing as main indications, and clinical main manifestations is that polydipsia, polyphagia, polyuria and health are become thin, i.e. typical " three-many-one-little " symptom.The high glucose of body persistence can bring disaster to body tissue, organ and cell, and causes the chronic complicating diseases such as diabetic nephropathy, diabetic foot, optical fundus and peripheral neuropathy, therefore, reduces the primary goal that body glucose level is treatment diabetes.Type 2 diabetes mellitus patient, except hyperglycemia, often shows as degradation symptom under impaired glucose tolerance, Ins sensitivity, exists lipid metabolic disorder and insulin tolerance abnormal simultaneously, and lab index shows as TC, TG, LDL rising, HDL reduction etc.
This experimental studies results shows, Radix Melandrii szechuanensis saponin can improve quickly and efficiently diabetic mice polydipsia, polyphagia symptom, reduces mouse blood sugar, promotes insulin secretion, increase the sensitivity of body to insulin, and can increase body tissue liver, muscle glycogen content, wherein, the pharmacodynamic action of compound 1 is similar to positive drug metformin, shows as the biologic activity of good blood sugar lowering, increase insulin sensitivity.Meanwhile, its pharmacodynamic action is held time long compared with metformin, can effectively prevent blood glucose bounce-back at short notice after drug withdrawal.Analyze its pharmacological activity effect, may be relevant with the reserve function that increases insulin secretion, enhancing insulin sensitivity and promotion body tissue human peripheral blood sugar.
Conclusion
Radix Melandrii szechuanensis saponin can significantly improve diabetic mice polydipsia, polyphagia symptom, effectively promote insulin secretion, obviously improve body insulin sensitivity, strengthen the glycogen reserve function of unit tissue, there is very strong hypoglycemic activity, be a kind of desirable active component for the treatment of diabetes, there is the good one-tenth property of medicine.
The blood sugar reducing function of experimental example 4 Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds to normal ICR mice
The compound 1 that the blood sugar reducing function of take is the strongest, compound 2 are representative, investigate the blood sugar reducing function of Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds to normal mouse.
Animal and feeding and management
(Beijing Si Beifu laboratory animal technology company limited provides 40 of 20～22g male ICR mouses, the quality certification number: SCXK(capital) 2011-0004) adaptability is fed after 1 week and carried out pharmacodynamic experiment.
Experimental animal feeding condition is as follows:
Table 6 experimental animal feeding condition
Temperature 22℃±2℃
Illumination
12 hours bright/12 are hour dark
Animal feeding is raised in box in the plastics that have bedding and padding, and the clean level of mice maintains feedstuff (Beijing section Australia pull together feed corporation,Ltd) and feeds, and freely drinks water.
Experimental design
Adaptability was fed after 1 week, and 40 ICR mices are divided into 4 groups at random, was respectively Normal group, 1 group of compound, 2 groups of compounds and positive drug metformin group, 10 every group.Each is organized the clean level of the equal feed of mice mice and maintains feedstuff.Normal group mouse subcutaneous injection water for injection, Radix Melandrii szechuanensis saponin is respectively organized the different saponin of mouse subcutaneous injection, positive drug metformin group gavage metformin aqueous solution, administration time is 9:00 every day left and right administration volume and is 10ml/kgBW.Continuous 2 weeks.
Measure weekly body weight and fasting glucose.
Grouping situation is as follows:
Table 7 animals administer and dosage
Grouping Administration Dosage (mg/kgBW)
Normal group Water for injection -
1 group of compound Compound 1 1
2 groups of compounds Compound 2 1
Positive drug metformin group Metformin 500
Medication
Compound 1, compound 2 are dissolved in sterile water for injection, filtration sterilization, every day subcutaneous injection, Normal group is only injected the water for injection of equal-volume (10ml/kg BW), metformin gastric infusion.Every morning 9 administrations, amount to 2 weeks.
Experimental program
The mensuration of body weight: measure weekly Mouse Weight one time.
The mensuration of blood glucose: measure weekly mouse blood sugar one time.Mice overnight fasting, cuts tail and gets blood, and test paper method is measured fasting glucose.
Experiment stops: administration finishes this experimentation after (14 days) in 2 weeks.
Data statistics: adopt SPSS10.0 software to carry out Data Management Analysis, all indexs all with mean ± standard deviation ( ) represent, between group, relatively adopt variance analysis.
Result
The impact of different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds on normal ICR Mouse Weight
Radix Melandrii szechuanensis saponin administration group mice compared with normal control group mice body weight is without significant change, and tables of data transparent tile grass saponin has no significant effect normal ICR weight of mice, as shown in figure 11.
The impact of different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds on normal ICR mouse blood sugar
After pharmaceutical intervention 1W, Radix Melandrii szechuanensis saponin group mouse blood sugar compared with normal matched group declines to some extent, and except 1 group of compound declines obviously (p<0.05), other respectively organizes mice only has decline to become, with Normal group comparison, no difference of science of statistics.Administration is in the time of 2 weeks, and 1 group of compound, 2 groups of mouse blood sugars of compound decline and more obviously (with Normal group ratio, p<0.01), show as obvious hypoglycemic activity, as shown in figure 12.
Conclusion
2 couples of intact animal of compound 1 and compound also have certain hypoglycemic activity, and this shows that Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds may produce certain influence to intact animal's blood glucose.
The blood sugar reducing function of the different Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds of experimental example 5 to experimental type 2 diabetes mellitus (T2DM) rat
Animal and feeding and management
(Si Beifu (Beijing) laboratory animal technology company limited provides 50 of 180～200g male SD rats, the quality certification number: SCXK(capital) 2011-0004) adaptability is fed after 1 week and carried out pharmacodynamic experiment.
Experimental animal feeding condition is as follows:
Table 8 experimental animal feeding condition
Temperature 22℃±2℃
Illumination
12 hours bright/12 are hour dark
Animal feeding is raised in box in the plastics that have bedding and padding, and the clean level of rat maintains feedstuff (purchased from Beijing section Australia feed corporation,Ltd that pulls together) and feeds, and freely drinks water.
Experimental design
Adaptability was fed after 1 week, and rat is divided into 5 groups at random, was respectively Normal group, model group, 1 group of compound, compound 2 and positive drug acarbose group, 10 every group.Each is organized the clean level of the equal feed of rat rat and maintains feedstuff.Normal group, model group mouse subcutaneous injection water for injection, Radix Melandrii szechuanensis saponin is respectively organized the different saponin of mouse subcutaneous injection, positive drug acarbose group gavage acarbose aqueous solution, administration time is 9:00 every day left and right administration volume and is 10ml/kgBW.Continuous 2 weeks.
Survey weekly body weight and fasting glucose.
Grouping situation is as follows:
Table 9 animals administer and dosage
Grouping Administration Dosage (mg/kg BW)
Normal group Water for injection -
Model group Water for injection -
1 group of compound Compound 1 4
2 groups of compounds Compound 2 4
Positive drug acarbose group Acarbose 20
Medication
Compound 1,2 is dissolved in sterile water for injection, filtration sterilization, every day subcutaneous injection, matched group, model group mice are only injected the water for injection of equal-volume (10ml/kg BW), acarbose gastric infusion.Every morning 9 administrations, amount to 2 weeks.
Experimental program
The preparation of T2DM model
60 rats are except 10 gavage animal drinking waters of normal group matched group, and all the other respectively organize the high lipoprotein emulsion of the equal gavage of rat, and 10ml/kg, weighs weekly.After surrounding, except normal group, each organizes equal lumbar injection streptozotocin (STZ, is dissolved in the citric acid-sodium citrate buffer of pH4.2, uses front preparation, keeps in Dark Place), 30mg/kg.After 4 days, tail venous blood sampling is surveyed blood glucose.Get the rat of fasting blood sugar >11.1mmol/L and include test in.
The mensuration of blood glucose
Respectively at before administration, administration is after 2 weeks, measures rat blood sugar.Rat overnight fasting, cuts tail and gets blood, and test kit method is measured fasting glucose.
Carbohydrate tolerance experiment (OGTT experiment)
OGTT experiment is carried out in administration after 2 weeks.Before experiment, rat fasting be can't help water 16h, 50% glucose subcutaneous injection rat, 5g/kgBW.Before subcutaneous injection glucose, first measure fasting blood sugar, after subcutaneous injection glucose 30,60,120min, measure respectively rat blood sugar.
The mensuration of fructosamine (GSP), hepatic glycogen, muscle glycogen content
When experiment finishes, abdominal aortic blood is measured GSP, is got part liver, skeletal muscle, and test kit method is measured liver/muscle glycogen content.
Experiment stops: administration finishes this experimentation after (14 days) in 2 weeks.
Data statistics
Adopt SPSS10.0 software to carry out Data Management Analysis, all indexs all with mean ± standard deviation (
Figure BDA0000424928050000232
) represent, between group, relatively adopt variance analysis.
Result
The impact of Radix Melandrii szechuanensis saponin on T2DM rat blood sugar
After administration 2 weeks, 2 groups of 1 group of compounds, compound obviously reduce (P<0.01) with the blood glucose of positive drug acarbose group rat compared with model group, show as good blood sugar reducing function, wherein, compound 1 blood sugar lowering intensity is better than positive drug acarbose, as shown in figure 13.
The impact of Radix Melandrii szechuanensis saponin on T2DM rat OGTT
When glucose 30min is raised in filling, each is organized rat blood sugar and all raises to some extent, and wherein, Normal group blood sugar increasing is not obvious, and model group and each administration group rat blood sugar sharply raise, and between administration group and model group, significant difference does not appear in blood glucose.When rats in normal control group blood glucose is raised glucose 30min in filling, blood glucose starts to decline, and when 120min, returns to normal level; Though model group rat blood sugar declines to some extent when 60min, 120min, decrease speed is slower, and during 120min, blood sugar level is still raised level before glucose higher than filling, shows as glucose tolerance and weakens; Pharmaceutical intervention group rat blood sugar decrease speed is obviously accelerated (with model group comparison compared with model group, p<0.05 or p<0.01), it is suitable with the effect of positive drug acarbose that compound 1, compound 2 improve the effect of diabetes rat OGTT, as shown in figure 14.
The impact of Radix Melandrii szechuanensis saponin on T2DM rats'liver glycogen, muscle glycogen and GSP Content
Model group liver, muscle glycogen content compared with normal matched group obviously reduce (P<0.05), and blood GSP content obviously increases (P<0.01).After compound 1, compound 2 and acarbose are intervened, each organizes Mouse Liver, muscle glycogen content all obviously increases, and blood GSP content obviously reduces, and wherein, compound 1, compound 2 effects obviously, are better than positive drug acarbose, as shown in Figure 15～17.
Discuss
The research of current domestic diabetes adopts streptozotocin (streptozotocin more, STZ) or alloxan large bolus injection prepare diabetes animal model, its mechanism of action is all selective injury pancreatic beta cell, cause necrocytosis, cause the blood insulin companion's blood sugar increasing that declines in various degree, multiform becomes type 1 diabetes, and the feature that its insulin secretion lacks and pathological process and the Clinical symptoms of type 2 diabetes mellitus (type2diabetes mellitus, T2DM) are not inconsistent.For this reason, by diet, in conjunction with the method for the pathogenic dosage streptozotocin lumbar injection in Asia, prepared T2DM model.
Each organizes the blood glucose value after modeling, compares all in obvious hyperglycemia state with blank group, illustrates that STZ makes hyperglycemia model success.
Experimental result shows, the blood sugar reducing function of compound 1 and compound 2 subcutaneous injection administrations is remarkable, and with the comparison of positive drug acarbose group, its hypoglycemic effect is all better than acarbose.
Hepatic glycogen and the muscle glycogen of T2DM diabetes rat model group all decrease, and 2 groups of hepatic glycogen of 1 group of compound and compound and muscle glycogen content are all apparently higher than Normal group, show that sinocrassuloside VI, VII can resist with the glycogenolysis of diabetes, obviously increase the glycogen content in liver and muscle, thereby the damage of opposing diabetes to liver and peripheral tissues, its effect is all better than positive control drug acarbose group.
On the amino of glucose and serum proteins molecule N-terminal under the high sugared state of diabetes, there is the stable polymer ketoamine structure that nonenzymatic glycosylation reacts formation in GSP.Because the sero-abluminous half-life is 17-20d, therefore, the mensuration of GSP can reflect measures the average blood sugar level of front 2-3 in week, not affected by instant blood sugar concentration.Measurement result demonstration, the numerical value of diabetes rat model group GSP obviously raises, and 1 group of compound, 2 groups of compounds and positive control acarbose group GSP value obviously reduce, compound 1 and compound 2 effects are all better than positive control acarbose.
Conclusion
Compound 1 and 2 subcutaneous injections have obvious blood sugar lowering, improve carbohydrate tolerance, increase liver/muscle glycogen content and reduce rat serum GSP effect, are a kind of effective subcutaneous injection blood sugar lowering bioactive ingredients.
These are only preferred embodiment of the present invention, not in order to limit the present invention, all within the present invention spirit and principle change, be equal to replacement, improvement etc., within being all included in protection domain of the present invention.

Claims (10)

1. Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is prepared the purposes of hypoglycemic drug, and the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure FDA0000424928040000011
Wherein, R 1a kind of in H, Ac, Glc;
R 2a kind of in (E)-MC, (Z)-MC, Ac;
R 3a kind of in H, Xyl;
R 4for H, CH 3, CH 2cH 2cH 2cH 3in a kind of;
The structural formula of above-mentioned Ac is as follows:
Figure FDA0000424928040000012
The structural formula of above-mentioned (E)-MC is as follows:
Figure FDA0000424928040000013
The structural formula of above-mentioned (Z)-MC is as follows:
Figure FDA0000424928040000014
2. Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds according to claim 1 is prepared the purposes of hypoglycemic drug, and the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure FDA0000424928040000021
3. Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds according to claim 1 is prepared the purposes of hypoglycemic drug, and the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure FDA0000424928040000022
4. Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds according to claim 1 is prepared the purposes of hypoglycemic drug, and the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
5. Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds according to claim 1 is prepared the purposes of hypoglycemic drug, and the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure FDA0000424928040000032
6. Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds according to claim 1 is prepared the purposes of hypoglycemic drug, and the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure FDA0000424928040000041
7. Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds according to claim 1 is prepared the purposes of hypoglycemic drug, and the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure FDA0000424928040000042
8. Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds according to claim 1 is prepared the purposes of hypoglycemic drug, and the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
9. Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds according to claim 1 is prepared the purposes of hypoglycemic drug, and the structural formula of described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds is as follows:
Figure FDA0000424928040000052
10. according to the arbitrary described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds of claim 1～9, prepare the purposes of hypoglycemic drug, described Radix Melandrii szechuanensis Pentacyclic triterpene saponins compounds can be used separately, two or more mixing is used or mixes use with other adjuvants, makes the injection, externally used solution agent, unguentum, paste, patch, drop, gargarism, suppository, sublingual tablet, sticking tablet, membranous patch, aerosol, effervescent tablet, the drop pill that use clinically.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015078133A1 (en) * 2013-11-28 2015-06-04 王学勇 Use of pentacyclic triterpenoid saponin compound from szechuan melandium root for preparing hypoglycemic drug
CN105147710A (en) * 2015-09-11 2015-12-16 中国科学院西双版纳热带植物园 Hypoglycemic agent as well as preparation method and application thereof
WO2015192758A1 (en) * 2014-06-16 2015-12-23 王学勇 Anti-tumor pharmaceutical application of pentacyclic triterpene saponin compounds of szechuan melandium root

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2596923B (en) * 2018-11-29 2022-12-14 January Inc Systems, methods, and devices for biophysical modeling and response prediction

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101817862A (en) * 2009-02-26 2010-09-01 中国药科大学 Ursolic acid-3-O-beta-D-pyranglucuronide and derivatives thereof, and preparation method and medicinal application thereof
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Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HONGZHENG FU 等: "Silenorubicosides A-D, Triterpenoid Saponins from Silene rubicunda", 《J. NAT. PROD.》 *
SHENGJUN GUO 等: "Characterization of some O-acetylated saponins from Quillaja saponaria Molina", 《PHYTOCHEMISTRY》 *
王童 等: "瓦草化学成分研究(I)", 《中国现代中药》 *

Cited By (4)

* Cited by examiner, † Cited by third party
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WO2015078133A1 (en) * 2013-11-28 2015-06-04 王学勇 Use of pentacyclic triterpenoid saponin compound from szechuan melandium root for preparing hypoglycemic drug
WO2015192758A1 (en) * 2014-06-16 2015-12-23 王学勇 Anti-tumor pharmaceutical application of pentacyclic triterpene saponin compounds of szechuan melandium root
CN105147710A (en) * 2015-09-11 2015-12-16 中国科学院西双版纳热带植物园 Hypoglycemic agent as well as preparation method and application thereof
CN105147710B (en) * 2015-09-11 2018-09-14 中国科学院西双版纳热带植物园 A kind of hypoglycemic drug and its preparation method and application

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